Recent insights into the effects of metabolism on breast cancer cell dormancy.

Breast cancer (BC) remains the most common cancer, as well as the leading cause of cancer mortality in women worldwide [1]. Approximately 30% of patients with early-stage BC experience metastasis or a recurrent form of the disease [2]. The phenomenon of BC dormancy, where metastasised cancer cells remain in a quiescent phase at their disseminated location and for unknown reasons can become actively proliferative again, further adds to BC's clinical burden with treatment at this secondary stage typically proving futile. An emerging avenue of research focuses on the metabolic properties of dormant BC cells (BCCs) and potential metabolic changes causing BCCs to enter/exit their quiescent state. Here we explore several studies that have uncovered changes in carbon metabolism underlying a dormant state, with conflicting studies uncovering shifts towards both glycolysis and/or oxidative phosphorylation. This review highlights that the metabolic states/shifts of dormant BCCs seem to be dependent on different BC subtypes and receptor status; however, more work needs to be done to fully map these differences. Building on the research that this review outlines could provide new personalised therapeutic possibilities for BC patients.

A Quiescent, Regeneration-Responsive Tissue Engineered Mesenchymal Stem Cell Bone Marrow Niche Model via Magnetic Levitation.

The bone marrow niche represents a specialized environment that regulates mesenchymal stem cell quiescence and self-renewal, yet fosters stem cell migration and differentiation upon demand. An in vitro model that embodies these features would open up the ability to perform detailed study of stem cell behavior. In this paper we present a simple bone marrow-like niche model, which comprises of nanomagnetically levitated stem cells cultured as multicellular spheroids within a type I collagen gel. The stem cells maintained are nestin positive and remain quiescent until regenerative demand is placed upon them. In response to coculture wounding, they migrate and appropriately differentiate upon engraftment. This tissue engineered regeneration-responsive bone marrow-like niche model will allow for greater understanding of stem cell response to injury and also facilitate as a testing platform for drug candidates in a multiwell plate format.

Gold nanoparticle-siRNA mediated oncogene knockdown at RNA and protein level, with associated gene effects.

AIMS: RNAi is a powerful tool for gene silencing that can be used to reduce undesirable overexpression of oncogenes as a novel form of cancer treatment. However, when using RNAi as a therapeutic tool there is potential for associated gene effects. This study aimed to utilize gold nanoparticles to deliver siRNA into HeLa cells. RESULTS: Knockdown of the c-myc oncogene by RNAi, at the RNA, protein and cell proliferation level was achieved, while also identifying associated gene responses. DISCUSSION: The gold nanoparticles used in this study present an excellent delivery platform for siRNA, but do note associated gene changes. CONCLUSION: The study highlights the need to more widely assess the cell physiological response to RNAi treatment, rather than focus on the immediate RNA levels.

The fibroblast response to tubes exhibiting internal nanotopography.

The use of three-dimensional scaffolds in cell and tissue engineering is widespread; however, the use of such scaffolds, which bear additional cellular cues such as nanotopography, is as yet in its infancy. This paper details the novel fabrication of nylon tubes bearing nanotopography via polymer demixing, and reports that the topography greatly influenced fibroblast adhesion, spreading, morphology and cytoskeletal organisation. The use of such frameworks that convey both the correct mechanical support for tissue formation and stimulate cells through topographical cues may pave the way for future production of intelligent materials and scaffolds.

Cell response to dextran-derivatised iron oxide nanoparticles post internalisation.

Magnetic nanoparticles have been used for many years as magnetic resonance imaging contrast agents. Despite the fact that there are currently several dextran-coated iron oxide nanoparticles are in preclinical and clinical use, there is very little information available concerning the influence such particles have on cells in culture. The prerequisite for particles employed as contrast agents is capture and subsequent uptake by cells. This study involved the use of magnetic nanoparticles synthesised and derivatised with dextran, compared to similar underivatised plain particles. The influence in vitro was assessed using human dermal fibroblasts and various techniques to observe cell-particles interaction, including light and fluorescence microscopy, scanning and transmission electron microscopy. The results indicate that although both the uncoated and the dextran-derivatised particles are uptaken into the cell, the derivatised particles induce alterations in cell behaviour and morphology distinct from the plain particles, suggesting that cell response is dependent on the particles coating.